Substituted pyridinium and piperidinium compounds



SUBSTITUTED PYRIDINIUM AND Aug., w, E943. R. s. sHELToN Erm. Y 2,446,792

PIPERIDINIUM COMPOUNDS Filed Aug. 28, 1943 3 Sheets-Sheet 2 DEC YL OcrYL HEPTYL /v-ALKYL @fem/p.

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C- A Tons nv SIDE CHA/N TOT/M C` Aro/v5 l/v 5/05 (HA/N -Hv- ALKYL AU M, E948. R. s. sHELToN Erm. 294459792 SUBSTITUTED PYRIDINIUM AND PIPERIDINIUM COMPOUNDS A Filed Aug. 28, 1W 3 Sheets-Sheet 3 5o M iff/YY1. A YL BUTXL /V- AL Kw. Greca/o, n

"2'- ALKYL "4"- Aun/4 Patented Aug. 10, 1948 SUBSTITUTED PYRIDINIUTK AND PIPER- IDINIUM COMPOUNDS Robert S. Shelton, Mariemont, and Marcus G. Van Campen, Jr., Deer Park, Ohio, assignors to The Wm. S. Merrell Company, Cincinnati, Ohio, a corporation of Delaware Applicationyaugm 2s, 1943, serial No. @0,340 21 claims, (ci. 26o- 295) This invention relates to compositions of matter for counteracting micro-organisms, generally referred to as germs, including bacteria. fungi, and the like; and especially to compositions suitable ior general use on inanimate objects as well as in treatment of wounds, skin and mucous surfaces, etc. Although the compositions of our invention will most often be used as germicides, i. e. for killing of such micro-organisms, they may also be used to inhibit growth of such organisms (bacteriostatic action) or to render germs more or less innocuous by a partial or complete nulliiication of their harmful eects or by inhibition of their normal activity which produces the harmful eiects. We refer to these various related uses generally, as germ-counteractingf,

Prior to our present invention it had been known that quaternary ammonium compounds of the type having one higher molecular aliphatic constituent on the ammonium nitrogen exhibit germicidal and bacteriostatic eects. In

. the prior patent of one of us, No. 2,295,504, it

. differentA compounds as cetyl trimethyl ammoni' um salts, cetyl tributyl ammonium salts, cetyl methyl piperidinium salts and cetyl pyridinium salts were all strikingly superior to the lauryl or stearyl homologues corresponding to any of these.

This generalization remains true with the substitution of a methyl group or groups on the pyridinium or piperidinium nucleus; but we have now discovered that surprisingly, when the length of the side chain on such a heterocyclic nucleus including quaternary ammonium nitrogen is increased, it begins to partake of and to modify the critical nature of the higher molecular constituent. The cetyl compounds maintain ltheir relatively higher activity up to the ethyl substitutions on a carbon atom of the heterocyclic nucleus; and the cetyl pyridinium compounds are made most active by such ethyl substitution. Beginning with the ethyl substitution on the N-alkyl compounds of the type mentioned, and becoming more evident with side chains of increasing lengths, two eects are introduced: rst the peaks of activity depend not upon the high molecular weight substituent alone, but

upon the sum of the carbon atoms in the high 'molecular weight substituent and in the side chain having at least 2 carbon atoms; and secondly, the peak activity bears a sharply critical relation to this sum of the carbon atoms in the y higher molecular weight group on the nitrogen and the lower molecular weight side chain on the heterocyclic nucleus, this peak appearing in the range from 16 to 18 carbon atoms. A minor anomaly appears when the respective substituent groups approach each other in number of C- atoms, the peak in such case usually appearing at 18 or 19 C-atoms, or in general in the range 1'7-19 C-atoms. Even in this case, however, highly active compounds below the peak activity occur in the range 16-18.

The high molecular weight radical attached to the ammonium nitrogen atom may be alkyl, alkenyl or acylated derivatives of alkyl and alkenyl radicals, e. g. of the COOR, OCOR., -CONHR types, wherein R is alkyl or alkenyl.

Additional surprising advantages are found for the compounds of this new type. In the i'lrst place, whereas the quaternary ammonium germicides generally have shown a substantial reduction of germicidal activity at temperatures substantially below body temperature, such as to require much higher concentration for germicidal solutions to be used on inanimate objects, such compounds when they have an alkyl side chain of several carbon atoms in length attached to one of the carbon atoms of the heterocyclic nucleus, not only reach a peak activity when the sum of the carbon atoms in said side chain plus those of the radical attached to the ammonium nitrogen is in the range stated, but this activity is better maintained at lower temperatures.

Moreover, in this range of anomalous activity, the activity of the compounds as against Gramnegative organisms (represented for example, by E. typhosa) rapidly comes abreast of the activity as against the Gram-positive organisms (represented by Staph. aureus); although with quaternary ammonium compounds in general it is substantially lower. At the peak activities the compounds of the present invention are usually at least as eective against the Gram-negative types as against the Gram-positive organisms and often are more active. Inasmuch as the organisms of the Gram-negative type are often considered to be of greater importance in the disinfection of inanimate objects, the relatively high activity as against these organisms, and more especially the equally high activity against both types of organisms. as well as the maintained activity at lower temperatures, are of great practical importance. Reference is also made to applicants copending applications Ser. No. 603,269 and Ser. No. 645,482, both containing related subject matter.

The toxicity of these compounds of our present invention is not increased as the activity against micro-organisms is increased. Thus there is a striking and extraordinary increase in the selective action against such micro-organisms in the presence of living tissues. As 4examples of this: N-lauryl 4-n-amyl pyridinium chloride injected intraperitoneally into mice, 2.5% aqueous solution 0.3 cc. per kg. of body weight killed only of the animals. The same dosage with N-n-amyl- 4-n-trldecyl pyridinium bromide and with N-nbutyl 4-n-tridecyl pyridinium bromide resulted in no deaths. All of these compounds show much lower toxicity with intravenous injection, and are even less toxic upon oral administration.

Due to the extraordinarily high activity of these compounds against pathogenic organisms at re1- atively low temperatures and to their low toxicity to the human organism, higher plants and animals, these compounds 4have been found particularly valuable for sterilization of drinking water, leafy vegetables and other foods and beverages which are likely to carry infection and are 'to be drunk or eaten without further cooking. ,Y

Likewise, due to the properties mentioned above and to the hygroscopic nature of these compounds, they are particularly advantageous for hospital and sick room sanitation. By washing room surfaces and particularly bed linens and bed clothing with a solution of these compounds, the surfaces are rendered antiseptic and by allowing a film of such solution to remain on these surfaces, airborne germs which may accumulate thereon are rendereded innocuous and the spread of infection by stirring up such germs during cleaning, bed-making, etc. can be largely avoided. Since these compounds are also soluble in oil and are powerful emulsifying agents, they may be applied for this purpose in oil emulsion, the oil .serving more eectively to catch and hold dust particles.

'I'hese same properties make the compounds of our invention very good for preservation of such substances as fruits. vegetables, other foods, clothing, shoes, wood and various organic sub- .,stances against attack by micro-organisms. in-

cluding insect larvae.

In the following table we have shown a number of examples of our invention. .A halogen analysis is included in this table since, in general. a variation from the calculated composition indicates the presence of tertiary amine salts or other relatively inactive substances which, if calculated as a quaternary ammonium compound, would, of course, reduce the apparent activity. It will be observed from this table that, in general, and except where impurity is noted under Remarks," the observed percentage of halogens conforms within the limits of high purity and experimental error with the calculated percentage.

For purposes of comparison it may be statedthat the homologous compounds beyond the specied range of our invention show much lower activities, their critical killing dilutions, in general, dropping to less than about 1:30,000 for E. typhosa and 1:50,000 for Staphylococcus aureus, at 37 C. When the sum of the carbon atoms in the high molecular weight substituent on the nitrogen atom and in the side chain of two or more carbon atoms on the heterocyclic nucleus amounts to from 16 to 18 carbon atoms, the activity (expressed as C.K. D.) is significantly increased to a peak ordinarily 50% or 100% or more higher than the activity of such compounds outside of the critical range.

It will also be observed that, whereas in general germicidal effectiveness is substantially reduced in -the presence of 10% serum at room temperature, in several cases the compounds having the peak activity also have surprising immunity to the presence of serum. y

Although the tests represented by this data have been carried out under carefully controlled conditions such that the data is believed to be adequate for forming comparisons and conclusions, it should be remembered that although the tests are made with standardized strains of the organisms, they still are living organisms which may vary from test to test in their resistance t-o germicidal compounds and also that the presence or absence of impurities may vary to some extent the exact gures obtained:

o. K. D. Eber. im H8105@ C. K. D. np Water Analysis sa I Auf MAM s 1 Compound p 's Point, 0- u' Remarks Bt 37 C. o 1 oC bultyy no serum 37 no 20 no 20 c8915 25 g serum 56mm serum cent cent N-Al lAmyl Pyridinium:

N- uryl 2namylpyr. Br.- 1 100M+ 1:90M+ 1:12M 25-30 1:5 21. 3 20.05 hygroscopic; 94%

. nrc. N-Lauryl 411-amylpyr. Br. 1:140M+ 1:130M+ 1:90M 1:13.500 85-87 1:35 20.0 20.05 hyPgrosoopic. N-Ialuxyl A-n-nliylpyr'. 01.--.- 1:130M+ 1:1Il)M+ 1:90M+ 1:18M+ 49-51. 1:30 9. 97 9. 98 Do. ery pyn mmm: Alllk-mur'l 2-hexy1 yr. Br. 1:69M 1:70M 76-78 1:5 19.33 19.38 Do.

N-Decy i-n-hexy pyr. Br.- 1:60M 1:90M 1:5 20. 7 20.8 hygroselopic; see other sam es. N-Lauryl 4nhexylpyn Br 1 100M+ 1:90M 1:14, 250 99-101 1:15 19. 25 19. 40 hygrospcopic. N -Alkyl Ethylpyridinium:

N-Cetyl 2ethylpyr. Br 1:100M+ 1:75M+ 1:30M 1:3M- 88-90 1:5 19.5 19. 4 Do. N-Myristyl 2ethylpyr. Br 1:100M+ 1190M+ 1:60M 1:3750 70-72 1:5 20. 35 20.30 Do. N-MynstyH-ethylpyr. BL--- 1:92M 1:130M+ 1:75M 1:6M 50-52 1:5 20.3 20.3 Do. N-Cetyl 4-ethylpyr. Br 1:90M+ 1:82M 1:30M- 1:3M 67-69 1:25 19. 3 19.4 N-Cety1 l-ethylpyr. Cl-g 1 100M+ 1:78%M 1:30M 1:3M- 67-70 1:5 9. 54 9.63 D0. VN-Alkyl Propyl pyridinium: N- l M+ 1:130M+ 1:90M 1:4500 64-67 1:5 19.9 20.1 Do.

Mynstyl 4ngaropylpyn Br a N -Alkyl Butyl yridinium: Y

N -Iuryl 4nbutylpyr. BL... 1:100M+ 1:90M 1:52M 1:6M 58-60 1:5 20. 7 20. 8 very hygroseopic. N -Mynstyl l-n-butylpyr. Br. -1:100M+ 1:90M+ 1:90M+ 1:4500 75-77 1:5 19. 0 19. 0 hlgngoplc; a hemiy te.

. .E Hams GKD. C K D ber Typhosa Water Analysis C stapel-1w. Melting soluompound s Point, Remarks at 37 C. 20010 C bility, b l no serum 37 no 20 no camper 25 (1)) ei' use? Serum serum serum cent cent N-Alkyl Nonyl pyridinium:

Ngi-OcJgy1-2-(2-methyloctyl) 1:67M 1:90M 65-67 1:5 19.9 20.0 hygroscopic.

yr. Ngly-DeylQ-(Z-methyloctyl) 1:100M-l 1:90M-l- 1:75M 1:3750 65-67 1:30 18.8 18.7 gellsat 1:5 conc.;

r. grosso ic. N-ngctyl 4-(2-methyloctyl) 1:100M 1130M+ 1:42%M 1:7%M 25 1:300 20.2 20.1 hygsr'oscopig.

p r. N-n-Dezyl 4-(2-methy1octyl) 1:100M+ 1:90M-l- 1:9750 25 1:600 18.8 18.75 Do.-

' pyr. r.

N-n-Lauryl 4-(2-methyloctyl) 1:80M 1135M 1:3M 25 1:1400 17.55 17.6 Do.

pyr. r. Nli-Decyl 4-(5-nonyl) pyr. 1:100M+ 1:110M 1:621/M lM oil 1:600 18.7 18.7

r. N-lauryl 4-(5-nonyl) pyr. Br 1:100M-l- 1:60M 1:30M oil 1:2M 17.6 17.6 Nra'i-Decyl 4-(n-nonyl) pyr. 1:100M+ 1:90M-l- 1190M+ 1:12M 1:500

N-Alkyl Uudecyl pyridinium:

N-n-AmylZ-n-undecylpyr. Br. 1:85M 1150M+ 1:61M-1182M 1:7%M 55-58 1:5 21.2 20.8 91% pure, hygroscopic. Nil-Eeptyl 2-n-undecylpyr. 1:130M+ 1130M+ 1:86M 114%M 65-08 1:5 19.7 19.4 95% pure N- 'Amyl4n-undecy1pyr.Br. 1:85M 1:75M 1:1354M 62-64 1:5 21.1 20.3 94% pure, hygrosco i Nrl-Hexyl 4-n-undecylpyr. 1:140M-l- 1130M 1:75M 1:12M 81-83 1:25 19.95 20.05 pure,p very hygror. sc 0.

N-Alkyl Tridecyl pyridinium: opl

Nn-Buty14-ntridecylpyr. Br. 1:120M 1140M+ 190Ml 1:11M 64-60 1:5 19.95 20.05 slightly hygroscopic. N-n-Amyl-i-n-tndecylpyr. Br. 1:100M+ 190M+ 1:90M-l- 1:9M i3-45 1:5 18.55 18.55 slightly hhylgroscopic;

mono y rate). N-n-Hexyl4-ntr1decylpyr. Br 1:100M+ 1:90M+ 1:90M+ 1:6M 97-98 1:20 18.7 18.7 slightly hygroscopic. N-Alkyl Ethyl iperidmium: N- 1:100M-l- 1:75M 1:50M 1:3Mf 83-85 1:10 18.1 18.1 ahemihydrate.

getyl-N-Met y1-2-ethy1piper.

r. N-Alkyl Amylpi ridinium: N- 1:135M-l- 1150M+ 1:88M 1:9M 250 1:20() 18.5 19.1

L auryl-N-Met yl-4-n-amylpiper. Br.

*M=103; +=actual value is higher,l dilution not exactly determined; =actual value is lower, dilution not exactly determined.

Although We have included in this table only 35 peratures. Alkyl chlorides are of course much-less halides in order to give basis for direct comparison, it should be understood that other salts are also active. The anion portion of the salt, whether organic or inorganic, should, of course, be one which gives a soluble salt and which is not of itself inconsistent wlth the use to be made of the salt or with other constituents with which it is to be used. Higher fatty acids generally are not desirable. Hydroxides are generally less stable and therefore less desirable than salts such as the halides.

In the accompanying drawings, Figs. 1, 2 and 3, we have charted available data for a series of compounds indicating definite test data by Xs for Staphylococcus aureus, Os for E.. typhosa at body temperature, lIs for E. typhosa at room temperature and As for E. typhosar at room temperature in the presence of serum, using arrows upwardly directed where values were determined only as above certain limits and downwardly directed arrows where they were determined only to be belowl the limits. We have also indicated for comparison the activities 0f some lhomologues of the various compounds next above and below the critical range. The heavy lines represent data. on Staphylococcus aureus at body temperature, the light lines, data on Eberthella typhosa at body temperature, the dash line shows data on E. typhosa at C. and the dot-dash line for E. typhosa at 20 C. in the presence of 10% serum.

From the charts the extraordinary increase in activity of the compounds of this type in the critical range is made strikingly evident.

Quaternary salts may be prepared readily from most 2, 3 or l1alkyl or dialkyl .pyridines by merely heating the appropriate pyridine compound with any primary alkyl halide at temperatures between 60 and 140 C. It is generally desirable to use as low a temperature as is convenient to avoid the side reactions which occur readily at higher temreactive than the bromides or iodides and therefore require higher reaction temperatures and/ol` longer reaction times. The alkyl pyridine will usually react readily at these temperatures, unless the alkyl residue is attached to the 2-position of the pyridine ring in which case the reaction may be sluggish and require several days even at the higher reaction temperatures. In case this-2- alkyl group is a stericaily large group such as the isopropyl or S-pentyl group, the attachment .of the alkyl halide to the pyridine nitrogen atom may be blocked' altogether if alkyl chlorides are used, and seriously interfered with even when the more reactive bromides and iodides are used.

The products obtained are often very hygroscopic and low melting, as well as very soluble in most solvents such as water, alcohol, acetone, and ether. For this reason, they are usually diicult to isolate in pure crystalline form. Specific details for the preparation of several characteristic compounds are given below:

N-Zauryl 4 n butylpyridinium bromide- A mixture of eqimolar parts of lauryl bromide and 4-n-butylpyridine are heated for 48 hours at 10D-110 C. The resulting thckoil is dissolved in about 2 volumes of ether, chilled to -20 C. and kept at this temperature overnight. The

crystalline material is quickly filtered, and dried ily in water to give clear 20% aqueous solutions.

N-n-amul-Z-n-undecylpudlnium' bromide-A in about two volumes of ether, chilled to -20 C. 5

and allowed to crystallize. 'I'he' product is nltered rapidly and dried in vacuo at a low temperature. The resulting solid is crystallized once more from ether to give a crystalline material,

M. P. 55-58, and very hygroscopic. It dissolves l0 readily to give clear aqeous solutions.

N-n-decul-4 n herulpvrdinium bromide-A mixture of equal molar parts oi.' n-decyl chloride and 4nhexylpyridine was heated at 110 C. for

65-70 hours. The product was dissolved in al- 15 cohol and decolorized with charcoal. The alcohol was thenl evaporated and the residual oil washed several times with anhydrous ether. The product was dried in vacuo over sulfuric acid.

The resulting oil resists attempts at crystalli- 20 zation, but contalnsthe theoretical amount of bromine.

N-lauryl 4 n amylpyrdinium chloride-A mixture of equal molar parts of lauryl chloride and 4namylpyridine are heated for 20 hours at 25 135. The resulting mixture is crystallized from ether at 20 C., iiltered rapidly and dried in vacuo at to 5 C. After a second recrystallization a pure crystalline product is obtained,

M. P. f1-50, which is extremely hygroscopic. It, 30

dissolves readily in water to give clear solutions at` or clear 2.5% solutions at 25.

N-n-butyl-4-n-trdecylpyridnium bromide-A mixture of 7l/2 parts of 4-n-tridecylpyridine and 3.9 parts of n-butyl bromide are heated at 75 35 somewhat hygroscopic, and very solublein wa.-

ter. Other tridecylpyridinium halides and other ring-substituted N-alkyl pyridiniums are preparedinananalogous manner. I

The same principles which govern the preparation of the pyridinium salts apply also to preparation of piperidinium salts, although the piperidinium salts are often less soluble, higher melting and easier to isolate. The preparation of a few typical examples is described in detail below:

mida-A mixture of equimolar parts of cetyl bromide and N-methyl-2-ethy1piperidine are heated at 110 for 8 hours. The product is crystallized twice from acetone, washed with ether and dried to give a product melting at 8385. The material 50 is readily soluble in water to give clear 10% solutions.

N-lauryl-N-methyl-i-n-amylppedinium bmmide.-A mixture of equimolar parts of lauryl bromide and N-methyl-l-n-amylpiperidine are 65 heated at-110 for 14 hours. The product was crystallized from acetone, washed with ether and dried to give a crystalline solid, M. P. 250 with decomposition. It is not readily soluble in water -but forms clear solutions in 1:50000 concentra- 70 bromide- A mixture of equimolar parts of N- methyl-2-n-hexyl piperidine and n-octyl bromide are heated at 110 :or 10 hours. The product is an 7 5 If de- 40 -oii which resists attempts atcrystailization. It

is purified by washing with dry ether several times to give anl oil soluble. in 5 parts of water' and containing 22.7% ,bromine. The-calculated y value is 22.4%. i

The alkenyl and aoylatedcompounds can made in similar manner using the corresponding alkenyl or acylated-hallde compounds for reacting with the substituted pyridlnes; and the alkenyl and acyl pyridines' may be used instead oi.' the alkyl pyridines. Examples of thepreparation of such compounds are:

N-cetyl-3-acetylpvridinium bromide-A mix ture of equimolar parts of cetyl bromide and 3- acetyl pyridine is heated at '15 -C. for about 15 hours. The resulting crude product may be puriiied by recrystallization from ether in the usual manner. The puriiied material is a hygroscopic. crystalline solid. Melting at -69. It forms a jell with 10 parts of water. and dissolves readily to form mobile aqueous solutions oi.' 1.0 to 0.5% concentration, Using myristyl bromide, the N- myristyl-S-acetyl-pyridinium bromide may be made, M. P. lOl-103 C., water solubility 1:5.

N-n-propyl-Z, 4-di-n-heptylm/ridinium bromide.-A mixture of equimolar parts of n-propyl bromide and 2,4-di-n-heptylpyridine are reiluxed or heated at 'l5-90 C. for several days until the reaction is at least complete as evidenced by a determination of ionizable bromine in the reactionl mixture. The product is then thoroughly washed with anhydrous ether to give an oily product, readily soluble in water to give clear solutions.

For ordinary germicidal and disinfecting purposes the compounds may be made up in water solutions of a strength, for example, 1:1,000 and diluted appropriately for the particular use to which it is to be put, or they may be furnished in more concentrated solution for appropriate dilution at the time of use. For treating hospital and sick room floors, walls, furniture and linen and patients bed clothing, etc., an emulsion may be made with any desired strength, e. g., 1:500 of the quater-nary ammonium compound, advantageously in accordance with the disclosure of the copending application of Manchey and Schneller, Serial No. 433,868, led March 9, 1942, now Patent No. 2,372,159.

For sterilization of drinking water, the compounds of our invention are advantageously made 4up in tablets of appropriate size for the container in which the Water is to be used. In view of the small amount of active compound required for such' sterilization, and in order to improve tableting and dissolution, it is ordinarily desirable to add a suitable diluent, for example, lactose. As one example, 45 parts of the N-alkyl alkyl pyridinium halide according to our invention is mixed with 50 parts of lactose and 5 parts of sugar syrup and this mixture is then formed into tablets of suitable size for dissolving in a canteen, jug, water barrel, or other container in which the water is to be sterilized, to give an eiective sterilizing strength of the active ingredients, e. g., 1:10,000 with4 the better of our compounds.

These compounds may also be used in place of other quaternary ammonium compounds in various known pharmaceutical `compositions and germicidal and disinfectant preparations. In particular th'ese compounds may be used in any of the formulae set forth. They may be used in aqueous or oleaginous compositions as well as in .organic solvents. They may be used in presence of acids or alkalies and with ilavoring, coloring,

therapeutic or many other types of ingredients. They may be used as indicated above for sterilization. or disinfection and they may be used for preservation of foods, clothing, wood, adhesives, biological materials, and in general wherever decomposition or putrefaction might occur. Illustrative of such compositions are:

These, of course, are only examples; and it should be understood that their proportions can Mouth wash Percent Germicide 0.1-.02 Boric acid 1 Alcoh'o1 20-30 Flavor as required Color as required Water q. s.

Skin antiseptic Percent Germicide .1-.5 Dye as required Alcohol 40-50 Water q. s. 100

Cough drops Percent Germicide .1 Aromatics as required Sugar q. s. 100

Lipstick Percent Germicide .l

Beeswax 33 Lard 12 Castor oil 41 Lanolin 4 Water 4 Perfume and color q. s as required v Dentifrice Percent Germicide 0.1

CaCO3 50 'I'ricalcium phosphate 25 Magnesium carbonate (or hydroxide) 24 Sugar saccharin and flavor 0.9 Wetting agent 0.1

Nose drops I Percent Germicide 0.03 Ephedrine S04 1 Dextrose 4 Water q. s 100 Germicidal ointment Percent Germicide 0.2 Petrolatum 69 Lanolin 25 Water v 6 Antiseptic medicated slainl cream Percent Germicide 0.1 Propylene glycol monostearate 10.0 Glycerin 5.0 Water 85.0

Lubricating jelly Percent Germicide 0.1 Tragacanth 1.0 Glycerin 15.0 Water 100 be varied substantially and that numerous other types of compositions are within the scope of the v monium compound in which the heterocyclic.

nucleus is a six-membered ring having tive carbon atoms and the ammonium nitrogen, and aliphatic radicals of more than two carbon atoms each are attached to the ammonium nitrogen and to at least one of the carbon atoms of said ring respectively, the sum of the carbon atoms of said radicals being at least 17 and less than 20 when one of said aliphatic radicals contains 9 or 10 carbon atoms and being at least 16 and less than 19 when none of said aliphatic radicals contains 9 or 10 carbon atoms.

2. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring having ve carbon atoms and the ammonium nitrogen, and having aliphatic radicals of more than two carbon atoms each attached to th'e ammonium nitrogen and to a carbon atom of said ring respectively, the sum of the carbon atoms of said radicals being 18 when one of said aliphatic radicals contains 9 or 10 carv bon atoms and being 17 when none of said aliphatic radicals contains 9 or 10 carbon atoms.

3. A germ-counteracting composition whichv comprises, as the essential germ--counteracting ingredient thereof, a heterocyclic Quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring having ve carbon atoms and the ammonium nitrogen, and having alkyl radicals of more than two carbon atoms each attached to the ammonium nitrogen and to at least one of the carbon atoms of said ring respectively and the sum of the carbon atoms of said alkylradicals being at least 17 and less than 20 when one of said alkyl radicals contains 9 or 10 carbon atoms and being at least 16 and less than 19 when none of said alkyl radicals contains 9 or 10 carbon atoms.

4. A germ-counteracting composition which comprises, asV the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring having ve carbon atoms and the ammonium nitrogen,l and alkyl radicals of more than two carbon atoms each attached to the ammonium nitrogen and to a carbon atom in the 2 position of said ring respectively and the sum of the carbon atoms of the attached radicals being at least 17 and less than 20 when one of said radicals contains 9 or 10 carbon atoms and being at least 16 and less than 19 when none of said alkyl radicals contains 9 or 10 carbon atoms.

comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in winch the heterocyclic nucleus is a six-membered ring having live carbon atoms and thev ammonium nitrogen, and alkyl radicals of more than two carbon atoms each attached to the ammonium nitrogen and to a carbon atom in the 4 position of said ring respectively and the sum of the carbon atoms of the attached radicals being at least 17 and less than 20 when one of said radicals contains 9 or 10 carbon atoms and being at least 16 and less than 19 when none of said alkyl radicals contains 9 or carbon atoms.

6. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of five carbon atoms and the ammonium nitrogen atom, the ammonium group including said nitrogen atom and an aliphatic radical, and a lower aliphatic radical of at least two carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms of all the radicals of at least two carbon atoms attached to said ring being at least 16 and less than 19.

7.' A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compond in which the heterocyclic nucleus is a siX-membered ring of five carbon atoms and the ammonium nitrogen atom, the ammonium group including said nitrogen atom and a higher aliphatic radical of more than ten carbon atoms, and a lower alkyl radical of at least two carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms of the radicals attached to the ring being at least 16 and less than 19.

8. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary am.. monium compound in which the heterocyclic nucleous is a six-membered ring of ve carbon atoms and the ammonium nitrogen atom, the ammonium group including said nitrogen atom and a higher aliphatic radical of more than ten carbon atoms, and a lower alkyl radical of at least two carbon atoms is attached to the carbon atom in la 2" position of the nucleus, the sum of the carbon atoms of the radicals attached to the ring being at least 16 and less than 19.

9. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of live carbon atoms and the ammonium nitrogen atom, the ammonium group including said nitrogen atom and a higher aliphatic radical of more than ten carbon atoms, and a lower alkyl radical of at least two carbon atoms is attached to the carbon atom in the 4 position of the nucleus, the sum of the carbon atoms of the radicals attached to said ring being at least 16 and less than 19.

10. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a pyridinium compound in which a higher aliphatic radical of more than ten carbon atoms is attached to the nitrogen atom of the pyridinium nucleus and an alkyl radical of at least two and less than eight carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms in said radicals being at least 16 and less than 19.

11. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a piperidinium compound in which a higher aliphatic radical of more than ten carbon atoms is attached to the nitrogen atom of the piperidinum nucleus and an alkyl radical of at least two and less than eight carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms in said radicals being at least 16 and less than 19.

12. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a N-higher alkyl ir-lower alkyl piperidinium compound, the sum of the carbon atoms in said higher and lower alkyl groups being at least 16 and less than 19.

13. A germ-counteracting composition which comprises as the essential germ-counteracting ingredient thereof, a N-lauryl 4-n-amyl pyridinium compound.

14. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a N-lauryl N-inethyl 4-n-amyl piperidinium compound.

15. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of live carbon atoms and the ammonium nitrogen atom, the ammonium group includes besides said nitrogen atom an aliphatic radical of at least two and less than nine carbon atoms and an aliphatic radical of at least eleven carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms of said radicals being at least 16 and less than 20.

16. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of ve carbon atoms and the ammonium nitrogen atom, the ammonium group includes besides said nitrogen atom an alkyl radical of at least two and less than nine carbon atoms, and an aliphatic radical of at least eleven carbon atoms is attached to a carbon atom of the nucleus, the sum of the carbon atoms of said radicals being at least 16 and less than 20.

17. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of ve carbon atoms and the ammonium nitrogen atom, the ammonium group includes besides said nitrogen atom an alkyl radical of at least two and less than nine carbon atoms, and an aliphatic radical of at least eleven carbon atoms is attached to the carbon atom in a 2 position of the nucleus, the sum of the carbon atoms of said radicals being at least 16 and less than 20.

18. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a heterocyclic quaternary ammonium compound in which the heterocyclic nucleus is a six-membered ring of five carbon atoms and the ammonium nitrogen atom, the ammonium group includes besides said nitrogen atom an alkyl radical of at least two and less than nine carbon atoms, and an aliphatic radical of at least eleven carbon atoms is attached to the carbon atom in the 4 position of the nucleus, the sum of the carbon atoms of said radicals being at least 16 and less than 20.

19. A germ-counteracting composition which comprises, as the essential germ-counteracting ingredient thereof, a pyridinium compound in which an alkyl radical of more than two and less than nine carbon atoms is attached to the nitrogen atom of the pyridinium nucleus, and a higher comprises, as the-essential germ-counteracting ingredient thereof, a N-butyl 4ntridecy1 pyridinium compound.

ROBERT S. SHELTON. MARCUS G. VAN CAMPEN, JR.

REFERENCES CITED The following references are of record in the 1 fue of this patent:

FOREIGN PATENTS Country Date Great Britain May 11, 1936 Number 

